Cyclodextrin chiral chromatographic stationary phase and preparation method thereof

Abstract

The invention discloses a cyclodextrin chiral chromatographic stationary phase and a preparation method thereof, and relates to the technical field of chromatographic separation.The cyclodextrin chiral chromatographic stationary phase is of a structure composed of polymer porous microspheres, NH2, cyclodextrin and o-didehydrobenzene, in the cyclodextrin chiral chromatographic stationary phase, a diluent is added into a mixed solution, the polymer porous microspheres can form true pores with the specific pore diameter during copolymerization, and the performance of the cyclodextrin chiral chromatographic stationary phase is improved. The stirring time is 10-20 minutes, and by controlling the stirring time, the specific pore diameter formed during copolymerization of the polymer porous microspheres can be controlled, so that the bonding amount of cyclodextrin is increased, and meanwhile, the rapid recognition performance of the stationary phase is improved; the polymer porous microspheres are cross-linked porous copolymers obtained by copolymerization of styrene and divinylbenzene, and cross-linking copolymerization can improve the temperature resistance of the carrier in the use of a chromatographic column; and introducing inert gas for 10-20 minutes, keeping the pressure in the reaction container at 100 kPa by introducing the inert gas, and keeping the reaction rate of the cyclodextrin with the polymer porous microspheres and the o-didehydrobenzene, so that the problem of low recognition speed of the cyclodextrin is solved.

Description

Technical Field

[0001] The invention relates to the technical field of chromatographic separation, and in particular to a cyclodextrin chiral chromatographic stationary phase and a preparation method thereof. Background Art

[0002] Cyclodextrin chiral chromatographic stationary phase is a special stationary phase used for separation of chiral compounds in chromatographic separation technology. It is made of cyclodextrin molecules or their derivatives fixed on the surface of chromatographic matrix (such as silica gel, polymer, etc.) by physical or chemical methods. Cyclodextrin molecules have special cavity structures and chiral characteristics, and can form inclusion complexes or produce other interactions with chiral molecules, thereby achieving effective separation of chiral compounds.

[0003] The bottleneck in the preparation of existing cyclodextrin chromatographic stationary phases is that cyclodextrin has a low bonding amount, slow recognition speed, and limited recognition ability, resulting in poor separation effects.

[0004] In summary, a cyclodextrin chiral chromatographic stationary phase and a preparation method thereof are designed. Summary of the invention

[0005] In order to overcome the above-mentioned shortcomings, the present invention provides a cyclodextrin chiral chromatographic stationary phase and a preparation method thereof.

[0006] The present invention achieves the above-mentioned purpose through the following technical solutions:

[0007] A cyclodextrin chiral chromatographic stationary phase is a structure composed of polymer porous microspheres, NH2, cyclodextrin and o-didehydrobenzene, wherein the mass ratio of the polymer porous microspheres to o-didehydrobenzene is 1:2-5, and the mass ratio of o-didehydrobenzene to cyclodextrin is 1:2-4.

[0008] A method for preparing the cyclodextrin chiral chromatographic stationary phase as described above comprises the following steps:

[0009] S1. The polymer porous microspheres are evenly placed in a mixed solution, and then a silanization agent is added, and the mixture is stirred at room temperature. The polymer porous microspheres are used as a stationary phase carrier, and water is used as a dispersed phase. A copolymer is synthesized by a silanization agent polymerization method. A diluent is added to the mixed solution, so that the polymer porous microspheres can form true pores with a specific pore size during copolymerization;

[0010] S2, filtering the mixture after the reaction in step S1, washing with water and ethanol respectively, and vacuum drying to obtain silanized polymer porous microspheres;

[0011] S3, uniformly dispersing the polymer porous microspheres, o-didehydrobenzene and cyclodextrin in step S2 in an organic solution, and passing an inert gas therein for 10-20 minutes;

[0012] S4, filtering and washing the mixture in step S3, and performing vacuum drying to obtain a product.

[0013] Preferably, in the step S1, the mixed solution is composed of a diluent, anhydrous ethanol, ammonia water and water, and the stirring time is 10-20 minutes. Here, by controlling the stirring time, the specific pore size formed by the polymer porous microspheres during copolymerization can be controlled to increase the bonding amount of cyclodextrin and improve the rapid recognition performance of the stationary phase.

[0014] Preferably, in step S1, the polymer porous microspheres are cross-linked porous copolymers obtained by copolymerization of styrene and divinylbenzene, and cross-linking copolymerization can improve the temperature resistance of such carriers in the use of chromatographic columns. Conventional silica spheres + cyclodextrin structures have low bonding degree and are not temperature resistant.

[0015] Preferably, in step S1, the silanization agent is one of trimethylchlorosilane, hexamethyldisilazane, tert-butyldimethylchlorosilane, triisopropylsilane, trimethylhydroxyethylsilane or methyldiphenylhydroxyethylsilane. The working principle of the silanization agent is mainly that the silyl group replaces the hydrogen atoms on the active group before the reaction, and the silyl group falls off and returns to its original state after the reaction.

[0016] Preferably, in step S2 and step S4, the ambient temperature of vacuum drying is controlled at 40-70°C.

[0017] Preferably, in step S3, the inert gas is one of nitrogen, helium or xenon, and the pressure in the reaction container is maintained at 100 kPa by introducing the inert gas.

[0018] Preferably, in step S3, the cyclodextrin is one of α-cyclodextrin, β-cyclodextrin and γ-cyclodextrin.

[0019] The beneficial effects of the present invention are as follows: in the cyclodextrin chiral chromatographic stationary phase and the preparation method thereof:

[0020] 1. Adding a diluent to the mixed solution can make the polymer porous microspheres form true pores with specific pore sizes during copolymerization. The stirring time is 10-20 minutes. Here, by controlling the stirring time, the specific pore size formed by the polymer porous microspheres during copolymerization can be controlled to increase the bonding amount of cyclodextrin and improve the rapid recognition performance of the stationary phase;

[0021] 2. The polymer porous microspheres are cross-linked porous copolymers obtained by copolymerization of styrene and divinylbenzene. Cross-linking copolymerization can improve the temperature resistance of this type of carrier in the use of chromatographic columns;

[0022] 3. Inert gas is introduced for 10-20 minutes. By introducing inert gas to maintain the pressure in the reaction container at 100 kPa, the reaction rate of cyclodextrin with polymer porous microspheres and o-didehydrobenzene can be maintained, thereby solving the problem of low recognition speed of cyclodextrin. DETAILED DESCRIPTION

[0023] The present invention will now be described in further detail.

[0024] A cyclodextrin chiral chromatographic stationary phase is a structure composed of polymer porous microspheres, NH2, cyclodextrin and o-didehydrobenzene, wherein the mass ratio of the polymer porous microspheres to o-didehydrobenzene is 1:2-5, and the mass ratio of o-didehydrobenzene to cyclodextrin is 1:2-4.

[0025] Embodiment 1:

[0026] A method for preparing the cyclodextrin chiral chromatographic stationary phase as described above comprises the following steps:

[0027] S1. The polymer porous microspheres are evenly placed in the mixed solution, and then a silanization agent is added, and the mixture is stirred at room temperature. The polymer porous microspheres are used as the stationary phase carrier, and water is used as the dispersed phase. The copolymer is synthesized by a silanization agent polymerization method. A diluent is added to the mixed solution, so that the polymer porous microspheres can form true pores with a specific pore size during copolymerization. The mixed solution is composed of a diluent, anhydrous ethanol, ammonia water and water. The stirring time is 10-20 minutes, and the silanization agent is trimethylchlorosilane;

[0028] S2, filtering the mixture after the reaction in step S1, washing with water and ethanol respectively, and vacuum drying to obtain silanized polymer porous microspheres;

[0029] S3, uniformly dispersing the polymer porous microspheres, o-didehydrobenzene and cyclodextrin in step S2 in an organic solution, introducing an inert gas for 10-20 min, and maintaining the pressure in the reaction container at 100 kPa by introducing the inert gas, wherein the cyclodextrin is α-cyclodextrin;

[0030] S4, filtering and washing the mixture in step S3, and performing vacuum drying to obtain a product.

[0031] Embodiment 2:

[0032] It is only necessary to replace the α-cyclodextrin in Preparation Example 1 with β-cyclodextrin and the trimethylchlorosilane with hexamethyldisilazane. Other operations are the same as in Example 1.

[0033] Embodiment 3:

[0034] It is only necessary to replace the α-cyclodextrin in Preparation Example 1 with γ-cyclodextrin and the trimethylchlorosilane with hexamethyldisilazane. Other operations are the same as in Example 1.

[0035] Embodiment 4:

[0036] It is only necessary to replace the α-cyclodextrin in Preparation Example 1 with γ-cyclodextrin and the trimethylchlorosilane with trimethylhydroxyethylsilane. The other operations are the same as in Example 1.

[0037] Embodiment 5:

[0038] It is only necessary to replace the α-cyclodextrin in Preparation Example 1 with β-cyclodextrin and the trimethylsilyl chloride with tris(triisopropyl)silyl oxide. The other operations are the same as those in Example 1.

[0039] The product obtained in Example 1 was used to prepare a chromatographic column. The filling method was a conventional method, and naphthalene was used to evaluate the column efficiency. The chromatographic column had a certain separation effect on phenolic compounds with similar structures. Similarly, after testing, Examples 2-5 all had a certain separation effect, and showed different separation selectivities.

[0040] The above is based on the present invention as an inspiration. Through the above description, relevant staff can make various changes and modifications without departing from the technical idea of ​​this invention. The technical scope of this invention is not limited to the content in the specification, and its technical scope must be determined according to the scope of the claims.

Claims

1. A cyclodextrin chiral chromatographic stationary phase, characterized in that: The structure is composed of polymer porous microspheres, NH2, cyclodextrin and o-didehydrobenzene, wherein the mass ratio of the polymer porous microspheres to o-didehydrobenzene is 1:2-5, and the mass ratio of o-didehydrobenzene to cyclodextrin is 1:2-4.

2. A method for preparing a cyclodextrin chiral chromatographic stationary phase according to claim 1, characterized in that: The following steps are involved: S1. Place the polymer porous microspheres evenly in the mixed solution, add the silanization reagent, and stir at room temperature; S2, filtering the mixture after the reaction in step S1, washing with water and ethanol respectively, and vacuum drying to obtain silanized polymer porous microspheres; S3, uniformly dispersing the polymer porous microspheres, o-didehydrobenzene and cyclodextrin in step S2 in an organic solution, and passing an inert gas therein for 10-20 minutes; S4, filtering and washing the mixture in step S3, and performing vacuum drying to obtain a product.

3. The method for preparing a cyclodextrin chiral chromatographic stationary phase according to claim 2, characterized in that: In the step S1, the mixed solution is composed of a diluent, anhydrous ethanol, ammonia water and water, and the stirring time is 10-20 minutes.

4. The method for preparing a cyclodextrin chiral chromatographic stationary phase according to claim 2, characterized in that: In the step S1, the polymer porous microspheres are cross-linked porous copolymers obtained by copolymerizing styrene and divinylbenzene.

5. The method for preparing a cyclodextrin chiral chromatographic stationary phase according to claim 2, characterized in that: In the step S1, the silanization agent is one of trimethylchlorosilane, hexamethyldisilazane, tert-butyldimethylchlorosilane, triisopropylsilane, trimethylhydroxyethylsilane or methyldiphenylhydroxyethylsilane.

6. The method for preparing a cyclodextrin chiral chromatographic stationary phase according to claim 2, characterized in that: In the steps S2 and S4, the ambient temperature of the vacuum drying is controlled at 40-70°C.

7. The method for preparing a cyclodextrin chiral chromatographic stationary phase according to claim 2, characterized in that: In the step S3, the inert gas is one of nitrogen, helium or xenon, and the pressure in the reaction container is maintained at 100 kPa by introducing the inert gas.

8. The method for preparing a cyclodextrin chiral chromatographic stationary phase according to claim 2, characterized in that: In the step S3, the cyclodextrin is one of α-cyclodextrin, β-cyclodextrin and γ-cyclodextrin.